title: Activation of 5-hydroxytryptamine1B/1D/1F receptors as a mechanism of action of antimigraine drugs.
abstract: BACKGROUND
  The introduction of the triptans (5-hydroxytryptamine (5-HT)1B/1D receptor agonists) was a great improvement in the acute treatment of migraine. However, shortcomings of the triptans have prompted research on novel serotonergic targets for the treatment of migraine.
  
  
  METHODS
  In this review the different types of antimigraine drugs acting at 5-HT receptors, their discovery and development are discussed. The first specific antimigraine drugs were the ergot alkaloids, consisting of ergotamine, dihydroergotamine and methysergide, which are agonists at 5-HT receptors, but can also bind α-adrenoceptors and dopamine receptors. In the 1990s, the triptans became available on the market. They are 5-HT1B/1D receptor agonists, showing fewer side effects due to their receptor specificity. In the last years, compounds that bind specifically to 5-HT1D, 5-HT1F and 5-HT7 receptors have been explored for their antimigraine potential. Furthermore, the serotonergic system seems to act in tight connection with the glutamatergic as well as the CGRP-ergic systems, which may open novel therapeutic avenues.
  
  
  CONCLUSIONS
  Although the triptans are very effective in treating migraine attacks, their shortcomings have stimulated the search for novel drugs. Currently, the focus is on 5-HT1F receptor agonists, which seem devoid of vascular side effects. Moreover, novel compounds that affect multiple transmitter and/or neuropeptide systems that are involved in migraine could be of therapeutic relevance.
authors.affiliation: Erasmus Medical Centre, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, The Netherlands.
authors.forename: Martha B
authors.initials: MB
authors.lastname: Ramírez Rosas
authors.forename: Sieneke
authors.initials: S
authors.lastname: Labruijere
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Villalón
authors.forename: Antoinette
authors.initials: A
authors.lastname: Maassen Vandenbrink
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D011985:Receptors, Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014363:Tryptamines / Q000627:therapeutic use*
chemical_list: D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D018698:Glutamic Acid; D015740:Calcitonin Gene-Related Peptide